Binuclear ruthenium(II) polypyridyl complexes: DNA cleavage and mitochondria mediated apoptosis induction

Binuclear complexes of the type [Ru2(N–N)4(TBPhen2)]4+, where N–N = 2,2’-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), dipyrido[3,2-a:2’,3’-c]phenazine (dppz) (3) and (TBPhen2) = bis-phenanthroline Tröger’s Base analogue, have been synthesized and characterized by 1H NMR, IR, UV–Vis, elemental analysis, ESI-Mass spectroscopy and cyclic voltammetry. The DNA binding characteristics of the complexes have been investigated by absorbance, steady-state emission, thermal melting and viscosity measurements. Photophysical studies reveal that [Ru2(TBPhen2)(dppz)4]4+ interacts with calf thymus DNA with an intrinsic binding constant of (8.75 ± 1.11 × 106 M−1). DNA cleavage studies of complexes 1–3 have been investigated using gel electrophoresis. The cytotoxicity of all the complexes against the HeLa cell line was evaluated by MTT assay and the status of mitochondria by real time living cell microscopy indicates apoptosis induction by complexes 1 and 2, further corroborated by a fluorescence microscopy–TUNEL assay.

Graphical abstractThe DNA binding, cleavage activity and cytotoxicity of complexes of the type [Ru2(NN)4(TBPhen2)]4+ against the HeLa cell line was evaluated by MTT assay, and the status of mitochondria by a real time living cell microscopy was investigated.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis and characterization of binuclear ruthenium(II) polypyridyl complexes. ► Interaction of complexes with CT-DNA. ► Investigation of the cytotoxicity against HeLa cells. ► Status of mitochondria by real time living cell microscopy.